[Tomography guided biopsy for the diagnosis of pediatric pulmonary Cryptococcosis]. / Punción Biopsia guiada por tomografía para el diagnóstico de Cryptococcosis pulmonar pediátrica.

Pulmonary cryptococcosis is a lung infection caused by the Cryptococcus yeast. It is rare in pediatrics, especially in immunocompetent children. The diagnosis of pulmonary cryptococcosis can be challenging due to the low specificity of symptoms, low index of suspicion, and limited diagnostic resources. OBJECTIVE: To describe a clinical case of pulmonary cryptococcosis in an immunocompetent adolescent, detailing the diagnostic approach. CLINICAL CASE: A 15-year-old patient, previously healthy, from a rural town, who consulted due to cough and a 1-month rib stitch pain, without fever or associated respiratory difficulty, with two images of condensation in the left lung on the chest x-ray. In the Computed Tomography, the images showed a nodular appearance. Due to suspicion of neoplastic pathology, a Positron Emission Tomography was performed, which showed hypermetabolic nodular lesions. The tomographic characteristics could correspond to fungal or granulomatous involvement. Considering the images and epidemiological risk factors such as rural origin and contact with bird droppings, the possibility of a mycosis was considered. A lung needle biopsy was performed under tomographic guidance. Cryptococcus neoformans was identified in the microbiology laboratory culture. The patient received treatment with itraconazole and fluconazole with good clinical and imaging response after 10 months of therapy and follow-up. CONCLUSION: In immunocompetent patients with a nonspecific clinical presentation, images can guide the diagnosis of pulmonary cryptococcosis, and an etiological search is essential to confirm it. In our case, the CT-guided needle biopsy was of great diagnostic utility.

Brain magnetic resonance imaging and computed tomography findings in cats and dogs with central nervous system cryptococcosis in Australia: 23 cases (2009-2020).

OBJECTIVE: To describe the imaging findings in Australian cats and dogs with CNS cryptococcosis. ANIMALS: 23 cases (10 cats; 13 dogs) with CNS cryptococcosis and brain MRI or CT studies available to review. METHODS: Retrospective, multi-institutional case series. Brain MRI or CT studies were reviewed by a board-certified radiologist. Imaging findings were described and the differences between cats and dogs explored. RESULTS: Morphologic features were consistent with extra-axial lesions in all (n = 13) dogs and either intra-axial (5/10) or extra-axial (4/10) lesions in cats, with 1 cat having no detectable lesions in low-field brain MRI scans. Meningeal abnormalities were most common, followed by forebrain and cerebellar lesions. Intracranial MRI lesions were typically T2 hyperintense and T1 hypo- to isointense. Four cases had T2 hypointense lesions affecting the brain, sinonasal cavity, or regional lymph nodes. Intracranial CT lesions were mostly soft tissue attenuating. Contrast enhancement was present in all cases with contrast series available, with ring enhancement shown only in cats. Osteolysis was more common in dogs than cats, particularly affecting the cribriform plate. All 13 dogs and many (6/10) cats had at least 1 lesion affecting sinonasal or contiguous tissues, and locoregional lymphadenomegaly was common (7/10 cats; 11/13 dogs). CLINICAL RELEVANCE: Imaging lesions in cryptococcal meningoencephalitis were extra-axial in dogs but could be intra-axial or extra-axial in cats. Careful examination for extracranial lesions (sinonasal, retrobulbar, facial soft tissue, tympanic bullae, or locoregional lymph nodes) is important to provide alternative safe biopsy sites. T2 hypointense lesions, while rare, should prompt consideration of cryptococcosis.

Pulmonary Cryptococcosis: Intense Uptake on Both 18 F-FDG and 68 Ga-FAPI PET/CT.

ABSTRACT: A 57-year-old woman without hepatitis B or immunodeficiency presented with right upper abdominal pain and cough for 3 months. CT revealed one nodule in the lung and another in the liver. Both 18 F-FDG and 68 Ga-FAPI PET/CT showed increased tracer uptake in these 2 nodules, suggesting pulmonary carcinoma with hepatic metastasis. Finally, biopsies of these 2 nodules demonstrated the diagnoses of hepatic adenocarcinoma and pulmonary cryptococcosis. This case highlights that cryptococcosis can be FAPI-avid.

Bioluminescence Imaging, a Powerful Tool to Assess Fungal Burden in Live Mouse Models of Infection.

Aspergillus fumigatus and Cryptococcus neoformans species infections are two of the most common life-threatening fungal infections in the immunocompromised population. Acute invasive pulmonary aspergillosis (IPA) and meningeal cryptococcosis are the most severe forms affecting patients with elevated associated mortality rates despite current treatments. As many unanswered questions remain concerning these fungal infections, additional research is greatly needed not only in clinical scenarios but also under controlled preclinical experimental settings to increase our understanding concerning their virulence, host-pathogen interactions, infection development, and treatments. Preclinical animal models are powerful tools to gain more insight into some of these needs. However, assessment of disease severity and fungal burden in mouse models of infection are often limited to less sensitive, single-time, invasive, and variability-prone techniques such as colony-forming unit counting. These issues can be overcome by in vivo bioluminescence imaging (BLI). BLI is a noninvasive tool that provides longitudinal dynamic visual and quantitative information on the fungal burden from the onset of infection and potential dissemination to different organs throughout the development of disease in individual animals. Hereby, we describe an entire experimental pipeline from mouse infection to BLI acquisition and quantification, readily available to researchers to provide a noninvasive, longitudinal readout of fungal burden and dissemination throughout the course of infection development, which can be applied for preclinical studies into pathophysiology and treatment of IPA and cryptococcosis in vivo.

Cryptococcus neoformans osteomyelitis of the tibia: a case report and review of the literature.

INTRODUCTION: Osteomyelitis is a bone inflammation that can be related to various infectious agents. As with any other type of inflammation, the prevailing symptoms and signs may include redness, swelling, pain, and heat. Fungal osteomyelitis is rare and usually found in immune-compromised patients. CASE PRESENTATION: A non-human immunodeficiency virus immunocompromised Greek female patient, 82 years old, visited the emergency department due to a 3 day pain located mainly over the left tibia's anterior surface, accompanied by swelling and redness. There was also a subcutaneous lesion of her left breast. Medical history revealed that the patient had an unmasked close contact with pigeons, a main host of the disease. Initial x-ray imaging showed an osteolytic area in the upper third of the tibial diaphysis. The patient was admitted and underwent a computed tomography-guided biopsy. The specimen revealed a Cryptococcus neoformans infection of the bone and the breast. She was treated with 400 mg fluconazole twice a day for 3 weeks while in hospital and 200 mg twice a day upon discharge for 9 months. After that, she underwent surgical debridement because of lasting local irritation. She was closely monitored in our outpatient office, and in her last visit, 1 year after the initial admission, inflammatory signs had regressed vastly. CONCLUSIONS: To our knowledge, this is the ninth cryptococcal osteomyelitis of the tibia to be recorded since 1974, and the most unusual finding was the bifocal nature of the infection, affecting both the tibia and the breast.

Lesion size as a prognostic factor in the antifungal treatment of pulmonary cryptococcosis: a retrospective study with chest CT pictorial review of 2-year follow up.

BACKGROUND: Pulmonary cryptococcosis (PC) is a fungal infection that can have a variable prognosis depending on several factors. The objective of this study was to analyse the characteristics of pulmonary lesions and identify prognostic factors in patients with PC who were human immunodeficiency virus (HIV) -negative and underwent antifungal treatment. METHODS: The study enrolled patients diagnosed with PC who were negative for HIV. Symptoms, CT characteristics of pulmonary lesions, serum cryptococcal capsular antigen (CrAg) titre, underlying diseases, and duration of antifungal treatment were evaluated over a 2-year follow-up. RESULTS: A total of 63 patients (40 men and 23 women) with a mean age of 50.4 years were included. Half of the patients (50.8%) were asymptomatic, and the most common symptoms were cough (44.4%), expectoration (27.0%), and fever (17.5%). Pulmonary lesions were mainly present in the peripheral and lower lobes of the lung, with 35 cases classified as nodular-type lesions and 28 cases classified as mass-type lesions. At the first, third, sixth, 12th, and 24th-month follow-ups, the median proportion of residual pulmonary lesions were 59.6%, 29.9%, 12.2%, 9.6%, and 0.0%, respectively. During antifungal treatment, the lesions of 33 patients achieved complete response, while the remaining 30 patients did not. Compared with the non-CR group, the CR group had a lower baseline serum CrAg titre (median, 1:20 vs 1:80, P < 0.01), smaller pulmonary lesion size (median area, 1.6 cm2 vs 6.3 cm2, P < 0.01), lower Hounsfield-units (HU) radiodensity (median, - 60.0 HU vs - 28.5 HU, P < 0.05), more nodular-type lesions (72.7% vs 36.7%, P < 0.01), and fewer air-bronchogram signs (18.2% vs 43.3%, P < 0.05). Multivariate logistic regression analysis showed that a larger lesion size on chest CT scans was associated with a lower likelihood of achieving complete response [OR: 0.89; 95% CI (0.81-0.97); P < 0.05]. CONCLUSIONS: PC was more commonly observed in HIV-negative men, and chest CT scans mostly revealed nodular-type lesions. After antifungal treatment, patients with smaller lesions had a better prognosis.

In vivo assessment of differences in fungal cell density in cerebral cryptococcomas of mice infected with Cryptococcus neoformans or Cryptococcus gattii.

In cerebral cryptococcomas caused by Cryptococcus neoformans or Cryptococcus gattii, the density of fungal cells within lesions can contribute to the overall brain fungal burden. In cultures, cell density is inversely related to the size of the cryptococcal capsule, a dynamic polysaccharide layer surrounding the cell. Methods to investigate cell density or related capsule size within fungal lesions of a living host are currently unavailable, precluding in vivo studies on longitudinal changes. Here, we assessed whether intravital microscopy and quantitative magnetic resonance imaging techniques (diffusion MRI and MR relaxometry) would enable non-invasive investigation of fungal cell density in cerebral cryptococcomas in mice. We compared lesions caused by type strains C. neoformans H99 and C. gattii R265 and evaluated potential relations between observed imaging properties, fungal cell density, total cell and capsule size. The observed inverse correlation between apparent diffusion coefficient and cell density permitted longitudinal investigation of cell density changes. Using these imaging methods, we were able to study the multicellular organization and cell density within brain cryptococcomas in the intact host environment of living mice. Since the MRI techniques are also clinically available, the same approach could be used to assess fungal cell density in brain lesions of patients.

Clinical and imaging characteristics of pulmonary cryptococcosis: a comparative analysis of 118 non-AIDS patients in China.

The accurate diagnosis of pulmonary cryptococcosis (PC) is an important guarantee for the selection of reasonable treatment methods. In this paper, the clinical and imaging manifestations of PC in non-AIDS patients were retrospectively analyzed, and according to whether there was an underlying disease, a comparative analysis was carried out to deepen the understanding of PC, and improve the accuracy of its diagnosis. Both clinical and CT imaging data of 118 PC patients were analyzed retrospectively. The clinical manifestations of PC patients were not specific, and 61 patients had no apparent symptoms. A total of 49 patients (49/118) were treated with antifungal agents alone, 46 of them had follow-up records after treatment, and 91.3% (42/46) of them achieved a good outcome. The most common imaging sign was the subpleural nodule or mass. Other main imaging signs include bronchial air sign (50/118), halo sign (32/118), ring target sign (65/118), lobulation sign (72/118), and necrosis (76/118). In terms of age, halo sign, and ring target sign, there were significant differences between the group with underlying disease and the group without underlying disease (P < .05). The CT manifestations of PC have some characteristics, and using antifungal agents can achieve good outcomes.

The CT manifestations of PC were characteristic. The subpleural lesions combined with bronchial air sign, ring target sign, and necrosis were important for the accurate diagnosis of PC. In addition, antifungal therapy for PC patients can achieve good results.

Disseminated cryptococcal infection with pulmonary involvement presenting as diffuse cavitary nodules in an immunocompromised patient: a case report.

BACKGROUND: Disseminated cryptococcal infection is especially prone to occur in immunosuppressed hosts. We herein report the case of an immunosuppressed girl with disseminated cryptococcal infection in whom pulmonary cryptococcosis (PC) presented as diffuse cavitary pulmonary nodules, a finding which has rarely been reported. CASE PRESENTATION: A 16-year-old immunocompromised girl presented with fever and a non-productive cough. A chest computed tomography (CT) scan revealed diffuse pulmonary nodules with cavities. Subsequent results were consistent with disseminated cryptococcosis with Cryptococcus identified in her blood, bone marrow and cerebrospinal fluid cultures. Thus, the patient was diagnosed with disseminated cryptococcal infection with PC, cryptococcus meningitis, cryptococcus osteomyelitis and cryptococcus sepsis. After antifungal treatment, the patient demonstrated both clinical and chest radiological improvement. CONCLUSION: The atypical clinical manifestations of a disseminated cryptococcal infection and the rare manner of chest CT findings of PC reported in our case are easy to misdiagnose. It is necessary to carry out a thorough search for a definitive diagnosis using various methods.

Disseminated cryptococcosis mimicking malignant lymphoma on 18F-FDG PET/CT: A case report.

RATIONALE: Disseminated cryptococcosis is extremely rare and is easily misdiagnosed as a malignant lymphoma. 18F-Fluorodeoxyglucose Positron Emission Tomography (PET)/ computed tomography (CT) may be useful to assess the involvement of disseminated cryptococcosis and to evaluate residual disease after treatment. PATIENT CONCERNS: A 21-years-old man presented with fever and cough for a month, with multiple red nodules scattered on the skin. 18F- Fluorodeoxyglucose PET/CT revealed multiple hypermetabolic lymph nodes in the upper and lower parts of the diaphragmatic region and hypermetabolic nodules in the skin. According to the PET/CT results, malignant lymphoma was considered a possibility, especially T-cell lymphoma involving the skin. DIAGNOSIS: Cryptococcosis was diagnosed using inguinal lymph node biopsy and blood culture. INTERVENTIONS: The patient received two months of amphotericin B, fluconazole, and half a month of meropenem. OUTCOMES: The patient's body temperature returned to normal and the red nodules on the skin disappeared. Most of the hypermetabolic enlarged lymph nodes disappeared, which was confirmed by reexamination with PET/CT. LESSONS: Disseminated cryptococcosis is easily misdiagnosed as malignant lymphoma, especially when the lymph nodes are more involved. When multiple hypermetabolic enlarged lymph nodes appear on PET/CT, except for lymphoma, specific infections should also be considered.

Comparison of the clinical manifestations and chest CT findings of pulmonary cryptococcosis in immunocompetent and immunocompromised patients: a systematic review and meta-analysis.

OBJECTIVE: The purpose of our study was to perform a meta-analysis and systematic review to compare differences in clinical manifestations and chest computed tomography (CT) findings between immunocompetent and immunocompromised pulmonary cryptococcosis (PC) patients. METHODS: An extensive search for relevant studies was performed using the PubMed, EMBASE, Cochrane Library, and Web of Sciences databases from inception to September 30, 2021. We included studies that compared the clinical manifestations and chest CT findings between immunocompetent and immunocompromised PC patients. Study bias and quality assessment were performed using the Newcastle-Ottawa Scale (NOS). RESULTS: Nine studies involving 248 immunocompromised and 276 immunocompetent PC patients were included in our analysis. The NOS score of each eligible study was above 5, indicating moderate bias. The proportion of elderly patients (> = 60 years old) in the immunosuppressed group was significantly higher than that in the immunocompetent group (OR = 2.90, 95% CI (1.31-6.43), Z = 2.63, p = 0.01). Fever (OR = 7.10, 95% CI (3.84-13.12), Z = 6.25, p < 0.000) and headache (OR = 6.92, 95% CI (2.95-16.26), Z = 4.44, p < 0.000) were more common in immunosuppressed patients. According to thin-section CT findings, lesions were more frequently distributed in the upper lobe (OR = 1.90, 95% CI (1.07-3.37), Z = 2.2, p = 0.028) in immunocompromised individuals. The proportions of patients with cavity sign (OR = 5.11, 95% CI (2.96-8.83), Z = 5.86, p = 0.00), ground-glass attenuation (OR = 5.27, 95% CI (1.60-17.35), Z = 2.73, p = 0.01), and mediastinal lymph node enlargement (OR = 2.41, 95% CI (1.12-5.20), Z = 2.24, p = 0.03) were significantly higher in immunocompromised patients. CONCLUSION: No significant differences in nonspecific respiratory symptoms were found between immunocompromised and immunocompetent PC patients. Nevertheless, fever and headache were more common in immunocompromised patients. Among the CT findings, cavity, ground-glass attenuation, and mediastinal lymph node enlargement were more common in immunocompromised individuals.

Establishment and evaluation of a CT-based radiomic model for AIDS-associated pulmonary cryptococcosis.

BACKGROUND: Establish a CT-based diagnostic radiomic model for AIDS complicated with pulmonary cryptococcosis and evaluate the diagnostic efficacy of this model. METHODS: This retrospective study enrolled 98 AIDS patients with pulmonary cryptococcosis and 103 AIDS patients with other infections or neoplastic lesions, comprising a total of 699 lesions. Patients were randomly divided into a training group and test group at a ratio of 2.75:1. Features from all lesions, cavity lesions and solid nodule lesions were extracted, and two kinds of radiomic models (6 types) were established. ROC curves were drawn, and the sensitivity and specificity were calculated to compare the SVM model and LR model, radiologists' empirical diagnoses and the combination of these empirical diagnoses with the radiomic model. RESULTS: The AUCs of senior radiologist for all lesions and cavity lesions were lower than those of the SVM and LR models. The diagnostic efficacy of primary radiologist was lower than that of both of the other model types. The diagnostic efficacy of the LR model was relatively stable, with the highest diagnostic efficiency of the 3 model/radiologist groups. The AUCs of intermediate radiologist in combination with the LR radiomic model for all lesions, nodular lesions and cavity lesions were 0.88, 0.84, and 0.9, respectively, which were the highest among all models and radiologists. CONCLUSIONS: The CT-based radiomic LR model of AIDS-associated pulmonary cryptococcosis exhibits good diagnostic performance, which was similar to that of senior radiologists and higher than that of the primary radiologist. With the help of a radiomic model, radiologists can achieve improved diagnostic accuracy compared to that when only an empirical diagnosis is used.

Computed tomography-based radiomics for identifying pulmonary cryptococcosis mimicking lung cancer.

BACKGROUND: Pulmonary cryptococcosis (PC) is an invasive pulmonary fungal disease, and nodule/mass-type PC may mimic lung cancer (LC) in imaging appearance. Thus, an accurate diagnosis of nodule/mass-type PC is beneficial for appropriate management. However, the differentiation of nodule/mass-type PC from LC through computed tomography (CT) is still challenging. PURPOSE: To develop and externally test a CT-based radiomics model for differentiating nodule/mass-type PC from LC. METHODS: In this retrospective study, patients with nodule/mass-type PC or LC who underwent non-enhanced chest CT were included: Institution 1 was for the training set, and institutions 2 and 3 were for the external test set. Large quantities of radiomics features were extracted. The radiomics score (Rad-score) was calculated using the linear discriminant analysis, and a subsequent fivefold cross-validation was performed. A combined model was developed by incorporating Rad-score and clinical factors. Finally, the models were tested with an external test set and compared using the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 168 patients (45 with PC and 123 with LC) were in the training set, and 72 (36 with PC and 36 with LC) were in the external test set. Of the 81 patients with PC, 30 were immunocompromised (37%). Rad-score, comprising 18 features, had an AUC of 0.844 after fivefold cross-validation, which was lower than that (AUC = 0.943, p = 0.003) of the combined model integrating Rad-score, age, lobulation, pleural retraction, and patches. In the external test set, Rad-score and the combined model obtained good predictive performance (AUC = 0.824 for Rad-score, and 0.869 for the combined model). Moreover, the combined model outperformed the clinical model in the cross-validation and external test (0.943 vs. 0.810, p <0.001; 0.869 vs. 0.769, p = 0.011). CONCLUSIONS: The proposed combined model exhibits a good differential diagnostic performance between nodule/mass-type PC and LC. The CT-based radiomics analysis has the potential to serve as an effective tool for the differentiation of nodule/mass-type PC from LC in clinical practice.

Clinical characteristics and image features of pulmonary cryptococcosis: a retrospective analysis of 50 cases in a Chinese hospital.

OBJECTIVE: To investigate the clinical manifestations and imaging characteristics of pulmonary cryptococcosis, and discuss its guidance in diagnosing. METHODS: The clinical data of patients diagnosed with cryptococcosis in our hospital from January 2014 to May 2020 were collected and retrospectively analyzed. Patients were divided into the immunocompromised group and the immunocompetent group. The symptomatic features, laboratory examination, imaging manifestations, and curative effect were analyzed. RESULTS: The most common symptoms of patients were cough and sputum production, followed by fever. The immunocompetent group has a significantly higher accident rate of cough and fever than the immunocompromised group, while the immunocompromised group has a significantly higher accident rate of headache and dizziness (P < 0.05). The positive rate of serum cryptococcal capsular antigen (CrAg) test of the two groups were 83.33% and 86.96%, respectively. While the positive rate of CrAg test in cerebrospinal fluid of the immunocompromised group was significantly higher than that of the immunocompetent group (P < 0.05). The lesions of pulmonary cryptococcosis were predominantly present in the lower part of the lung periphery and significantly distributed in the right lung (P < 0.05). The most common imaging finding of pulmonary cryptococcosis was halo sign (64.58%), followed by multiple nodules, and trachea sign was significantly more common in the immunocompetent group. CONCLUSIONS: Cryptococcosis has an insidious onset, which can infect healthy people as well. Conducting a CrAg test is good for screening and diagnosing cryptococcosis. We should be alert for the high risk of cryptococcal meningoencephalitis in patients with compromised immune function.

Disseminated Cryptococcus neoformans infection diagnosed by endoscopic ultrasound guided fine needle aspiration (EUS-FNA).

A 34-year-old woman was admitted to the hospital because she had an intermittent fever for two months. The patient had a history of contact with pigeons. She had no human immunodeficiency virus (HIV) infection, and her physical examination was normal. Computed tomography of the abdomen revealed intrahepatic bile duct dilatation and multiple retroperitoneal lymphadenopathies, and the largest enlarged lymph node was in hepatic hilum.

CT findings of nasal cryptococcosis in cats and dogs: A case series.

Cryptococcus spp. can cause chronic rhinitis in cats and dogs. Computed tomography (CT) descriptions of imaging features of nasal cryptococcosis are limited. This retrospective single-center consecutive case series aimed to describe the CT features of lesions in cats and dogs with nasal cryptococcosis. Ten cats and 12 dogs with a diagnosis of nasal cryptococcosis confirmed with cytology, histopathology, and/or serology that had undergone a head CT from 2010 and 2020 were included. Images were evaluated by a veterinary radiologist for the presence of a nasal or nasopharyngeal mass, regional destruction, intracranial extension, and lymphadenopathy. The majority of cats (8/10 [80%]) had nasal lesions with most cases described as non-destructive rhinitis (7/8 [88%]). Three cats (3/10 [30%]) had a nasal mass. All cats had a nasopharyngeal mass, and in most cases (8/10 [80%]) the nasopharyngeal mass was centered caudally near the temporomandibular joints. None of the cats had cribriform plate lysis or meningeal enhancement. All dogs had nasal lesions. Eleven dogs (11/12 [92%]) had destructive rhinitis with lysis of nasal conchae. Most dogs (8/12; 67%) had a nasal mass, of which in seven dogs the caudal nasal mass extended into the rostral nasopharynx. Most dogs had cribriform plate lysis (9/12 [75%]), of which four dogs (44%) had mass extension into the cranium. Our findings support potential differences in CT features between dogs and cats with nasal cryptococcosis. Nasal cryptococcosis should be considered a differential diagnosis in dogs and cats with nasal and nasopharyngeal masses.

Diagnosis and treatment of cryptococcal osteomyelitis in a pediatric lung transplant patient.

BACKGROUND: Asymptomatic pulmonary nodules may appear at any point after lung transplantation. The differential diagnosis is broad and includes serious life-threatening disease entities. METHODS: A retrospective case report of a single patient who developed a pulmonary nodule after lung transplantation. RESULTS: At 2 years post-transplant, an 11-year-old with cystic fibrosis was asymptomatic and had normal lung function. A single nodule was noted on surveillance chest CT scan. Initial evaluation was negative, but subsequently, he was diagnosed with cryptococcal osteomyelitis in a thoracic rib. He responded well to an extended course of antifungal therapy without loss of allograft function or infectious complications. CONCLUSION: Pulmonary nodules after lung transplantation may be a harbinger of serious complications. A systematic approach to evaluation and follow-up is recommended.